Staphylococci:

Introduction
groups of medically important gram-positive cocci. Staphylococcal infections range from the trivial to the rapidly fatal. They can be very difficult to treat, especially those contracted in hospitals, because of the remarkable ability of staphylococci to become resistant to antibiotics. The most virulent of the genus, Staphylococcus aureus, is one of the most common causes of bacterial infections, and is also an Staphylococci are members of the Micrococcaceae family. They are classically considered extracellular, pyogenic pathogens because of their ability to induce abscess formation. The bacteria are nonmotile and tend to grow in clusters. They areextremely hardy and can survive for prolonged periods of time on environmental surfaces. This family includes Staphylococcus aureus, epidermidis and saprophyticus. The initial descriptions below refer to the most important pathogen of this family - Staphylococcus aureus. Staphylococci and streptococci constitute the mainimportant cause of food poisoning and toxic shock syndrome. Among less virulent staphylococcal species, Staphylococcus epidermidis is an important cause of prosthetic implant infections, whereas Staphylococcus saprophyticus causes urinary tract infections, especially cystitis in women.
Staphylococci generally stain darkly gram positive. They are round rather than oval and tend to occur in bunches like grapes. Because growth of staphylococci requires supplementation with various amino acids and other growth factors, they are routinely cultured on enriched media containing nutrient broth and/or blood Staphylococci are facultatively anaerobic organisms. They produce catalase, which is one feature that distinguishes them from the catalase- negative streptococci. Pathogenic staphylococci are commonly identified by their ability to produce coagulase, and thus clot
blood .This distinguishes the coagulase positive strains, S. aureus (a human pathogen), and S. intermedius and S. hyicus (two animal pathogens), from the other staphylococcal species such as S. epidermidis, that are coagulase-negative (CoNS) . Staphylococci are hardy, being resistant to heat and drying, and thus can persist for long periods on fomites (inanimate objects), which can then serve as sources of infection. Frequent handwashing before and after contact with food or potentially infected individuals decreases the transmission of staphylococcal disease
STAPHYLOCOCCUS AUREUS
Generally, significant host compromise is required for S. aureus infection, such as a break in the skin or insertion of a foreign body (for example, wounds, surgical infections, or central venous catheters), an obstructed hair follicle (folliculitis), or a compromised immune system. S. aureus disease may be: 1) largely or wholly the result of actual invasive infection, overcoming host defense mechanisms, and the production of extracellular substances which facilitate invasion; 2) a result of toxins in the absence of invasive infection (“pure” toxinoses); or 3) a combination of invasive infection and intoxication . S. aureus is frequently carried by healthy individuals on the skin and mucous membranes. Carriers serve as a source of infection to themselves and others; for example, by direct contact, by contamination of fomites (objects such as doorknob, which in turn can be a source of infection) or contamination of food, which can then result in food poisoning.
Pathogenesis
Virulence factors are the genetic, biochemical, or structural features that enable an organism to produce disease. The clinical outcome of an infection depends on the virulence of the pathogen and the opposing effectiveness of the host defense mechanisms. S. aureus expresses many potential virulence factors.

1. Cell wall virulence factors:
a. Capsule: Most clinical isolates express a polysaccharide “microcapsule” of Types 5 or 8. The capsule layer is very thin but has been associated with increased resistance to phagocytosis. Clinical isolates produce capsule but expression is
rapidly lost upon in vitro cultivation.
b. Protein A: Protein A is a major component of the S. aureus cell wall. It binds to the Fc region of IgG, exerting an anti-opsonin (and therefore strongly antiphagocytic) effect.
c. Fibronectin-binding protein: Fibrinectin-binding protein (FnBP) and other staphylococcal surface proteins promote binding to mucosal cells and tissue matrices.
d. Clumping factor A: or ClfA, is a virulence factor from S. aureus that binds to fibrinogen.ClfA also has been shown to bind to complement regulator I protein.It is responsible for the clumping of blood plasma observed when adding S. aureus to human plasma. Clumping factor can be detected by the slide test.

2. Cytolytic exotoxins: ?, ?, ?, and ? Toxins attack mammalian cell (including red blood cell) membranes, and are often referred to as hemolysins. ? Toxin is the best studied, and is chromosomally encoded. It polymerizes into tubes that pierce membranes, resulting in the loss of important molecules and, eventually, in osmotic lysis.
3. Panton-Valentine leukocidin: This pore-forming toxin lyses PMNs. Production of this toxin makes strains more virulent. This toxin is produced predominantly by community-acquired methicillin-resistant S. aureus (MRSA) strains
4. Superantigen exotoxins: These toxins have an affinity for the Tcell receptor–major histocompatibility complex Class II antigen complex. They stimulate enhanced T-lymphocyte response (as many as 20 percent of T cells respond, compared with 0.01 percent responding to the usual processed antigens). This difference is a result of their ability to recognize a relatively conserved region
of the T-cell receptor. This major T-cell activation can cause toxic shock syndrome, primarily by release into the circulation of inordinately large amounts of T-cell cytokines, such as interleukin-2 (IL- 2), interferon-? (IFN-?), and tumor necrosis factor-? (TNF-?).
a. Enterotoxins: Enterotoxins (six major antigenic types: A, B, C, D, E, and G) are produced by approximately half of all S. aureus isolates. When these bacteria contaminate food and are allowed to grow, they secrete enterotoxin, ingestion of
which can cause food poisoning. Enterotoxins are superantigens that are even more heat-stable than S. aureus. organisms are not always recovered from incriminated food but the toxin may be recovered.
b. Toxic shock syndrome toxin (TSST –1): This is the classic cause of toxic shock syndrome (TSS). Because of similarities in molecular structure, it is sometimes referred to as staphylococcal enterotoxin F, although it does not cause food poisoning when ingested.
c.. Exfoliatin (exfoliative toxin, ET)
proteases that split desmoglein 1 of the intercellular bridges in epidermis; produced by about 5-10% of S. aureus; causes the generalized desquamation of the staphylococcal scalded skin syndrome (SSSS).
Clinical significance
S. aureus causes disease by infecting tissues, typically creating abscesses and/or by producing toxins. A common entry point into the body is a break in the skin, which may be a minute needles tick or a surgical wound. Another portal of entry is the respiratory tract. For example, staphylococcal pneumonia is important complication of influenza. The localized host response to staphylococcal
infection is inflammation, characterized by swelling, accumulation of pus, and necrosis of tissue. Fibroblasts and their products may form a wall around the inflamed area, which contains bacteria and leukocytes. This creates a characteristic pus-filled boil or abscess. Serious consequences of staphylococcal infections occur
when the bacteria invade the bloodstream. The resulting septicemia (the presence and persistence of pathogenic microorganisms or their toxins in the blood) may be rapidly fatal. Bacteremia (the presence of viable bacteria circulating in the bloodstream) may result in seeding internal abscesses, skin lesions, or infections in the lung, kidney, heart, skeletal muscle, or meninges.
1. Localized skin infections: The most common S. aureus infections are small, superficial abscesses involving hair follicles (folliculitis) or sweat or sebaceous glands. For example, the common sty (external hordeolum) is created by infection of an eyelash follicle. Subcutaneous abscesses called furuncles (boils) often form around foreign bodies such as splinters. These generally respond to local therapy, that is, removal of the foreign body, soaking, and drainage as indicated. Carbuncles are larger, deeper, multiloculated skin infections that can lead to bacteremia and require antibiotic therapy and debridement. Impetigo is usually a localized, superficial, spreading crusty skin lesion generally seen in children. It can be caused by S. aureus, although more commonly by Streptococcus pyogenes, or both organisms together. Human staphylococcal infections usually remain localized at the portal of entry by normal host defenses.
2. Deep, localized infections: These may be metastatic from superficial infections or skin carriage or may result from trauma. S. aureus is the most common cause of acute and chronic infection of bone marrow. S. aureus is also the most common cause of acute infection of joint space in children (septic joint). They must be treated promptly with drainage and an antibiotic.
3. Acute endocarditis: Generally associated with intravenous drug abuse, acute endocarditis is caused by injection of contaminated preparations or by needles contaminated with S. aureus. S. aureus also colonizes the skin around the injection site, and if the skin is not sterilized before injection, the bacteria can be introduced into soft tissues and the bloodstream, even when a sterilized needle is used. An abscess in any organ or tissue is cause to suspect S. aureus, although many other bacteria can cause abscesses.
4. Septicemia is a generalized infection with sepsis or bacteremia that may be associated with a known focus (for example, a septic joint) or not .
5. Pneumonia: S. aureus is a cause of severe, necrotizing pneumonia
6. Nosocomial infections: S. aureus is one of the most common causes of hospital-associated infections, often of wounds (surgical, decubital) or bacteremia associated with catheters .
7. Toxinoses: These are diseases caused by the action of a toxin, frequently when the organism that secreted the toxin is undetectable. Toxinoses caused by S. aureus include:
a. Toxic shock syndrome: TSS results in high fever, rash (resembling a sunburn, with diffuse erythema followed by desquamation), vomiting, diarrhea, hypotension, and multiorgan involvement (especially GI, renal, and/or hepatic damage). An outbreak of TSS occurred in the late 1970s among
women.. .
b. Staphylococcal gastroenteritis: This is caused by ingestion of food contaminated with enterotoxin-producing S. aureus. Often contaminated by a food handler, these foods tend to be protein rich (for example, egg salad or cream pastry) or salty, like ham (S. aureus is salt tolerant), and improperly refrigerated. These heat-resistant toxins are able to withstand subsequent reheating. Symptoms, such as nausea, vomiting, and diarrhea, are acute following a short incubation period (less than 6 hours) and are triggered by local actions of the toxin on the GI tract rather than from infection. for a summary of foodborne illness. The short incubation period of staphylococcal food poisoning occurs because the toxin in the food has already been formed by the staphylococci before the food is ingested.
c. Scalded skin syndrome: This involves the appearance of superficial bullae resulting from the action of an exfoliative toxin that attacks the intercellular adhesive of the stratum granulosum, causing marked epithelial desquamation .
Laboratory identification
Identification of an isolate as a staphylococcus relies largely on microscopic and colony morphology and catalase positivity .Bacteria stain strongly gram-positive, and are frequently seen in grapelike clusters .S. aureus is distinguished from the coagulase-negative staphylococci primarily by coagulase positivity. In addition, S. aureus colonies tend to be yellow (hence “aureus,” meaning golden) and hemolytic), rather than gray and nonhemolytic like the coagulase-negative staphylococci. S. aureus is also distinguished from most coagulase-negative
staphylococci by being mannitol-positive.

Treatment
In most patients who require surgical treatment, antibiotic treatment is also required. Incision and drainage of pus is the main surgical treatment; however, surgical removal of sources of infection (for example, intravenous lines, artificial grafts, heart valves, or pace makers) may be required. Other sites of infection, such as joint infections (especially in children), osteomyelitis, or postoperative abscesses, may require surgery. Antibiotics, doctor may perform tests to identify what type of staph bacteria is behind the infection, and to help choose the antibiotic that will work best. Antibiotics commonly prescribed to treat staph infections include certain cephalosporins, nafcillin or related antibiotics, sulfa drugs or vancomycin.
Vancomycin is required to treat serious staph infections because so many strains of staph bacteria have become resistant to other traditional medicines. But vancomycin and some other antibiotics have to be given intravenously.
Hospital-acquired S. aureus infections are now resistant to penicillin G due to penicillinase-encoding plasmids or transposons. This has required the replacement of the initial agent of choice, penicillin G, by ?-lactamase-resistant penicillins, such as methicillin or oxacillin. However, increased use of methicillin and related antibiotics has resulted in S. aureus that is resistant to a number of ?-lactam antibiotics, such as methicillin, oxacillin and amoxicillin. These strains are known as methicillin-resistant



Prevention
There is no effective vaccine against S. aureus. Infection control procedures,
such as barrier precautions and disinfection of hands and fomites, are important in the control of nosocomial S. aureus epidemics..


COAGULASE-NEGATIVE STAPHYLOCOCCI


Of 12 coagulase-negative staphylococcal species that have been recovered as normal commensals of human skin and anterior nares, the most abundant and important is S. epidermidis. For this reason some clinical laboratories designate all coagulase-negative staphylococci as S. epidermidis, a practice that is not encouraged. The second most important coagulase-negative staphylococcus is S. saprophyticus, which has a special medical niche. Coagulase-negative staphylococcal species are important agents of hospital-acquired infections associated with the use of implanted prosthetic devices and catheters.

A. Staphylococcus epidermidis
S. epidermidis is present in large numbers as part of the normal flora of the skin. As such, it is frequently recovered from blood cultures, generally as a contaminant from skin. Despite its low virulence, it is a common cause of infection of implants such as heart valves and catheters. Acquired drug resistance by S. epidermidis is
even more frequent than by S. aureus. Vancomycin sensitivity remains the rule, but vancomycin-resistant isolates have been reported. S. epidermidis produces an extracellular polysaccharide material called polysaccharide intercellular adhesin (sometimes called “slime”), that facilitates adherence to bioprosthetic material surfaces, such as intravenous catheters, and acts as a barrier to antimicrobial agents.


B. Staphylococcus saprophyticus
This organism is a frequent cause of cystitis in women, probably related to its occurrence as part of normal vaginal flora. It tends to be sensitive to most antibiotics, even penicillin G. S. saprophyticus can be distinguished from S. epidermidis and most other coagulase-negative staphylococci by its natural resistance to novobiocin